Mechanical stress activates proinflammatory cytokines and antioxidant defense enzymes in human dental pulp cells.
This study was conducted to investigate the effects of mechanical stress, particularly cyclic strain, on proinflammatory cytokines as well as antioxidant properties and their interactions with cellular defense systems in human dental pulp (HDP) cells. Exposure of HDP cells to mechanical strain induced inflammatory cytokines such as interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-6, as well as antioxidant genes such as heme oxygenase-1, superoxide dismutases, reduced nicotinamide adenine dinucleotide phosphate quinone oxidoreductase-1, and glutathione peroxidases. In addition, treatment with N-acetylcysteine, indomethacin, and heme oxygenase-1 inhibitors blocked reactive oxygen species production, antioxidant response element (ARE) gene expression, and Nrf2 accumulation that occurred in response to mechanical stress. These data demonstrate that mechanical strain activates inflammatory cytokines and oxidative stress, which then act in concert to induce the Nrf2-/ARE-mediated antioxidant enzymes. Therefore, we suggest that the activation of a compensatory adaptation or defense antioxidant system might represent a novel mechanism for protecting HDP cells against mechanical stress.
Lee
Sun-Kyung
SK
Department of Oral and Maxillofacial Pathology, College of Dentistry, Wonkwang University, Iksan, Republic of Korea; Sun-Kyung Lee and Kyung-San Min contributed equally to this work.
Min
Kyung-San
KS
Department of Conservative Dentistry, College of Dentistry, Wonkwang University, Iksan, Republic of Korea; Sun-Kyung Lee and Kyung-San Min contributed equally to this work.
Kim
Youngho-
Y
Department of Biochemistry, College of Medicine, Wonkwang University, Iksan, Republic of Korea.
Jeong
Gil-Saeng
GS
Institute for Radiological Imaging Science, College of Oriental Medicine, Wonkwang University, Iksan, Republic of Korea.
Lee
Seung-Hoon
SH
Department of Oral and Maxillofacial Pathology, College of Dentistry, Wonkwang University, Iksan, Republic of Korea.
Lee
Hwa-Jeong
HJ
Department of Oral and Maxillofacial Pathology, College of Dentistry, Wonkwang University, Iksan, Republic of Korea.
Lee
Sang-Im
SI
Department of Oral and Maxillofacial Pathology, College of Dentistry, Wonkwang University, Iksan, Republic of Korea.
Kim
Young-Suk
YS
Department of Oral and Maxillofacial Pathology, College of Dentistry, Wonkwang University, Iksan, Republic of Korea.
Lee
Young-Man
YM
Department of Oral and Maxillofacial Pathology, College of Dentistry, Wonkwang University, Iksan, Republic of Korea.
Park
Sung-Joo
SJ
Department of Herbology, College of Oriental Medicine, Wonkwang University, Iksan, Republic of Korea.
Seo
Sang-Wan
SW
Department of Herbology, College of Oriental Medicine, Wonkwang University, Iksan, Republic of Korea.
Lee
Suk-Keun
SK
Department of Oral and Maxillofacial Pathology, College of Dentistry, Kangnung National University, Kangnung, Republic of Korea.
Kim
Eun-Cheol
EC
Department of Oral and Maxillofacial Pathology, College of Dentistry, Wonkwang University, Iksan, Republic of Korea. Electronic address: eckwkop@wonkwang.ac.kr.
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D019610:Cytoprotection / Q000502:physiology*; D003782:Dental Pulp / Q000166:cytology / Q000378:metabolism*; D003799:Dental Stress Analysis; D004790:Enzyme Induction; D015870:Gene Expression; D005979:Glutathione Peroxidase / Q000096:biosynthesis; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis; D018384:Oxidative Stress; D011808:Quinone Reductases / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D020218:Response Elements / Q000502:physiology; D013314:Stress, Mechanical; D013482:Superoxide Dismutase / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D051267:NF-E2-Related Factor 2; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D005979:Glutathione Peroxidase; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; C041831:NADH dehydrogenase (quinone); D011808:Quinone Reductases